EEG-cholinergic Index and Clinical Response to Treatment With Cholinesterase Inhibitors (Cholindex)

August 16, 2018 updated by: Landspitali University Hospital

EEG-cholinergic Index and Its Validation of Clinical Response to Treatment With Cholinesterase Inhibitors

Drug treatment with cholinesterase inhibitors is indicated for treatment of Alzheimer´s disease and in most cases, one of these drugs is prescribed as soon as the diagnosis has been made. Nevertheless, it has been shown in several studies that up to 30% of patients do not benefit from treatment. These drugs can have side effects, most frequently from the gastrointestinal tract with nausea, diarrhea and discomfort in the abdomen as the most frequent signs. It is therefore important to know before the treatment is initiated if the patient will likely benefit from the drug or not. It is not possible today with current knowledge but this project aims to evaluate a specific index, calculated from an EEG registration (the EEG-cholinergic index) for this purpose. A conventional EEG registration is done before treatment and the cholinergic index calculated from the EEG registration is compared to the clinical outcome. The duration of follow up is 6 months with an extension of further 6 months.

Study Overview

Status

Unknown

Detailed Description

Patients will be recruited in a Memory Clinic. Three possible groups of participants will be offered participation:

  • Those with Mild Cognitive Impairment (MCI) but with biomarkers of Alzheimer´s disease (AD) that are conclusive enough to lead to the diagnosis of AD and to initiate medical treatment.
  • Those with early dementia of AD that are offered medical treatment and are able to give consent.
  • Those with early dementia of Lewy body dementia or Parkinson dementia that are offered medical treatment.

All eligible participants are evaluated by the Mini Mental State Examination (MMSE), Consortium to Establish Registry in Alzheimer´s Disease (CERAD 10 word test; working memory, delayed memory and recognition) and Clock Drawing Test (CDT). In addition, the Addenbrooke test will be used.

Patients with AD irrespective of stage will be offered treatment with donepezil, the most used and cheapest cholinesterase inhibitor in Iceland. The dosis will be as usual, 5mg in the evening for four weeks, then increased to 10mg in the evening.

Patients with Lewy body dementia and Parkinson dementia are offered rivastigmine in patch as this is the only medication with the indication of cognitive impairment in these disorders. The starting dose is 4.6mg/day increased to 9.5mg/day after 4 weeks.

After 3 months, each participant is evaluated again with the same tests as before initiating treatment (continuous variables). The clinical effect is also rated according to Clinical Dementia Rating (CDR; categorical variables). An EEG registration is performed. Adherence to drug therapy as well as evaluation of side effects is registrated.

After 6 months, each participant is evaluated again as after 3 months. This is the primary end point.

After 12 months an additional evaluation is performed by the same instruments (secondary endpoint).

The EEG is thus registrated 3 times (primary end point) or 4 times (secondary end point as the first registration was done during the diagnostic work up before entering the project. The EEG will reveal group wise category (Normal, AD or Lewy according to the third edition (SIGLA) of Mentis Cura). An analysis of the cholinergic index is not revealed to the clinician that is thus blinded to this part of the EEG analysis.

The project will be analysed based on all available information after primary end point. A second analysis will be performed after the second end point.

Study Type

Observational

Enrollment (Actual)

218

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Individuals diagnosed at a Memory Clinic with Mild Cognitive Impairment or mild dementia due to Alzheimer´s disease or with dementia due to Lewy body disease

Description

Inclusion Criteria:

  • Mild Cognitive Impairment or mild dementia due to Alzheimer´s disease or with dementia due to Lewy body disease.

Exclusion Criteria:

  • Too advanced dementia (5 or more on Global Deterioration Scale)
  • likelihood of poor compliance due to social circumstances, drug or alcohol abuse or other defined causes.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
MCI due to Alzheimer´s disease
Individuals with MCI diagnosed with Alzheimer´s disease on the basis of cognitive decline and positive biomarkers by MRI and/or Cerebro Spinal Fluid (CSF) analysis. The intervention is donepezil in recommended doses, 5mg/day for a month and then 10mg/day. Cholinergic index in EEG will be measured before initiating treatment, after 3 and 6 months and related to clinical response of treatment
Mild dementia due to Alzheimer´s disease
Individuals with mild dementia and diagnosed with Alzheimer´s disease on the basis of cognitive decline and positive biomarkers by MRI and/or CSF analysis. The intervention is donepezil in recommended doses, 5mg/day for a month and then 10mg/day. Cholinergic index in EEG will be measured before initiating treatment, after 3 and 6 months and related to clinical response of treatment
Mild dementia due to Lewy body disease
Individuals with mild Lewy body dementia. The intervention is Exelon patches in recommended doses, 4.6mg/day for a month and then 9.5mg/day. Cholinergic index in EEG will be measured before initiating treatment, after 3 and 6 months and related to clinical response of treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in Addenbrooke cognitive battery at 3 months and at 6 months
Time Frame: Baseline, 3 months, 6 months
Addenbrooke cognitive battery will be used before initiating treatment (baseline), after 3 months and after 6 months
Baseline, 3 months, 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mini Mental State Examination (MMSE)
Time Frame: Baseline, 3 months, 6 months
MMSE will be used before initiating treatment (baseline), after 3 months and after 6 months
Baseline, 3 months, 6 months
CERAD-10 word test
Time Frame: Baseline, 3 months, 6 months
CERAD-10 word test will be used before initiating treatment (baseline) after 3 months and 6 months
Baseline, 3 months, 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Jon Snaedal, MD, Professor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (ANTICIPATED)

May 1, 2019

Study Completion (ANTICIPATED)

November 1, 2019

Study Registration Dates

First Submitted

November 5, 2015

First Submitted That Met QC Criteria

December 3, 2015

First Posted (ESTIMATE)

December 8, 2015

Study Record Updates

Last Update Posted (ACTUAL)

August 17, 2018

Last Update Submitted That Met QC Criteria

August 16, 2018

Last Verified

August 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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